For pulmonary delivery of aerosols and dry powders, delivered dose is difficult to predict and estimate. Deposition in the lungs is driven by numerous factors, including for example particle size, depth of inspiration, residence time, and lung condition.
Metered dose inhalers (MDIs), dry powder inhalers (DPIs), and nebulizers currently address the bulk of applications for pulmonary delivery of aerosols and dry powders. FDA guidance documents on MDIs and DPIs estimate that only about 10% -15% of dose reaches the biological target. The remainder is trapped in the mouth and pharynx and swallowed or is exhaled. Inhalers for delivering medicament to pulmonary systems historically can delivery fairly accurate amounts of inhalant in the form of an aerosol. More specifically, inhalers generally accurately generate a mist of inhalant for the patient to breathe into their pulmonary system. One issue is with whether the patient properly breathes in the inhalant being generated. A second issue is how much aerosol is expelled during an out-breath. Both issues will vary from patient to patient, making predictability and control of proper dosage difficult.
Delivery of particulates to the deep pulmonary regions of the lung, the alveoli, can be optimized by delivering particles of the proper size range and by increasing residence times. For alveoli deposition, particles with diameters in the range of about 1 to 3 microns appear optimal. Particles below approximately 3 microns in diameter have been shown, via scintigraphy studies, to be preferentially transported to the deep lungs, whereas larger particles tend strike the throat or rain out in the bronchial passages. Smaller particles penetrate more deeply but also have an increased tendency to be exhaled. Therefore, for deep pulmonary delivery systems exhalation of particles can be substantial issue.
Some devices for deep pulmonary delivery attempt to optimize delivered dose and delivered dose reproducibility by measuring inhalation and exhalation rates and delivering the drugs at critical points. While these small particle size systems with active measurement of breathing maneuvers should help to ensure more reproducible dosing, there are still many uncontrolled factors affecting deposition and eventual bioavailability.